The proposed project is to study factors controlling the proliferation and maturation of hematopoietic stem cells in vivo and in vitro. The major emphasis is directed toward the study of in vitro proliferation of granulocyte-macrophage and megakaryocyte progenitor cells (CFU-GM, CFU-M) from the marrow of animals and man. Progenitor cells are cultured in a soft gel system (agar or methylcellulose) in the presence of a colony stimulating activity (CSA). In addition, cells will be cultured long term in liquid suspension. Studies will be directed toward the following: 1) to study the mechnaisms of lithium induced granulocytosis, 2) to delineate factors controlling the proliferation of megakaryocytes and megakaryocyte progenitor cells, 3) to determine the virus-cell interaction in cytomegalovirus infection, 4) to determine the pattern of proliferation of hematopoietic progenitor cells in leukemia, preleukemia, and myelofibrosis.